IFR128 BioSciences Gerland - Lyon Sud
U851 INSERM-UCBL "Immunité, Infection, Vaccination"
Immunité des muqueuses, vaccination et tolérance.

Responsable d'équipe :
Dominique KAISERLIAN
Adresse :
INSERM U851
21 avenue Tony Garnier
69365 Lyon Cedex 07
Téléphone :
 + 33 (0)4 37 28 23 94
Fax :
 + 33 (0)4 37 28 23 91
E-mail :
 dominique.kaiserlian@inserm.fr
Research projects :

The research projects of the team are focused on the mechanisms of induction and regulation of immune responses, generated by penetration and/or delivery of model antigens, (allergens and vaccines) via mucosal tissues and skin.

The team is specialized in the development of animal models of patho-physiological relevance to allergic and inflammatory diseases and models suitable for the in vivo testing anti-infectious vaccines. The team is also devoted to development of clinical studies in human. These include pathophysiological studies of chronic allergic and inflammatory diseases affecting the intestine (food allergy, Crohn disease, IPEX) and the skin (contact dermatitis) and therapeutic clinical studies on the safety and efficacy of novel routes of vaccination against infectious diseases.

In recent years the main advances include the following areas:
 

(i) Dynamics and function of dendritic cells in skin and mucosal epithelia. We have shown that dendritic cells (DC) recruited in pluristratified mucosal epithelia and derived from circulating monocytes, are responsible for presentation of vaccine antigens and allow for in vivo cross priming of CD8 CTL in vivo. The CCR6/CC20 pathway plays a key role in the efficacy of adjuvants to induce such CD8 CTL responses.

(ii) Mechanisms of oral tolerance to environmental and food antigens. We have shown that regulatory CD4+ T cells are required for oral tolerance and prevent systemic DTH responses mediated by CD4 and CD8+ T cells. We have identified the immunosuppressive potential of plasmacytoid DC and the crucial role of liver pDC in the induction of oral tolerance.

(iii) Role of CD8+ T cells in chronic inflammatory bowel diseases. We have We developed news models of colitis in mice showing that gut inflammation results from a DTH response to self and environmental antigens, mediated by CD8+ T cells. IFNg-producing cytotoxic CD8 CTL initiate relapsing colitis and upon migration to the colon can induce cytolysis of epithelial cells. This indicates that in IBD, CD8 may come before CD4 to initiate the inflammatory cascade.

(iv) Mucosal vaccination for CD8+ CTL priming. Danger signals provided by adjuvants or pathogens administered via mucosal or skin sites allow for initiation of systemic as well as mucosal immunity. A clinical study in healthy human volunteers shows that topical vaccination against measles using a patch is able to induce measles-specific mucosal IgA .
 
Main publications :
  • Dubois B, Joubert G, de Agüero MG, Gouanvic M, Goubier A, Kaiserlian D.
    Sequential Role of Plasmacytoid Dendritic Cells and Regulatory T Cells in Oral Tolerance. Gastroenterology. 2009 Apr 1. [Epub ahead of print]
  • Goubier A, Dubois B, H. Gheit, Joubert G, Villard-Truc F, Asselin-Paturel C, Trinchieri G & Kaiserlian D.
    Plasmacytoid dendritic cells are responsible for oral tolerance.
    Immunity. 2008 Sept 29(3):464-75.
  • Etchart N, Hennino A, Friede M, Dahel K, Dupouy M, Goujon-Henry C, Nicolas JF, Kaiserlian D.
    Safety and efficacy of transcutaneous vaccination using a patch with the live-attenuated measles vaccine in humans.
    Vaccine. 2007 Sep 28;25(39-40):6891-9
  • S. Nancey, S. Holvöet, I. Graber, G. Joubert, D. Philippe, S. Martin, JF. Nicolas, P. Desreumaux, B. Flourié and Kaiserlian D.
    CD8 cytotoxic T cells induce relapsing colitis in normal mice.
    Gastroenterology 2006. 131(2):485-96.
  • Marie Le Borgne, Nathalie Etchart, Anne Goubier, Sergio A. Lira, Jean Claude Sirard , Nico van Rooijen, Christophe Caux, Smina Aït-Yahia, Alain Vicari, Dominique Kaiserlian and Bertrand Dubois.
    Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8 T cell cross-priming in vivo.
    Immunity.     2006. 24 : 191-201.
  • Kissenpfennig A, Henri S, Dubois B, Laplace-Buihle C, Perrin P, Romani N, Tripp CH, Douillard P, Leserman L, Kaiserlian D, Saeland S, Davoust J, Malissen B.
    Dynamics and function of Langerhans cells in vivo dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells.
    Immunity.     2005. 22(5):643-54.
  • Tomasello E, Desmoulins PO, Chemin K, Guia S, Cremer H, Ortaldo J, Love P, Kaiserlian D & Vivier E.
    Combined Natural Killer Cell and Dendritic Cell Functional Deficiency in KARAP/DAP12 Loss-of-Function Mutant Mice.
    Immunity, 2000, 13: 355-64
  • Dubois B, Chapat L, Goubier A, Papiernik M, Nicolas JF and Kaiserlian D.
    Innate CD4CD25 regulatory T cells are required for oral tolerance and control CD8 T cells mediating skin inflammation.
    Blood     2003. 102: 3295-3301.
  • Etchart N, Desmoulins PO, Chemin K, Maliszewski C, Dubois B, Wild F, Kaiserlian D.
    Dendritic cells recruitment and in vivo priming of CD8+ CTL induced by a single topical or transepithelial immunization via the buccal mucosa with measles virus nucleoprotein.
    J Immunol. 2001 Jul 1;167(1):384-91.

 

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